25.14 : 胰高血糖素样受体激动剂

Oral glucose intake triggers gut hormones like GLP-1 and GIP called incretins, which stimulate insulin secretion.

Both GLPs and glucagon originate from the preproglucagon. Proglucagon is processed into a large peptide including glucagon or GLP-1 and GLP-2, by intestinal L cells and specific hindbrain neurons.

However, GLP-1 is degraded by DPP-4 and endopeptidases and excreted renally, making it therapeutically unsuitable.

To circumvent this, metabolically stable GLP-1 analogs, including dulaglutide, liraglutide, and lixisenatide, have been developed.

These drugs help improve glycemic control in type 2 diabetes patients, either alone or combined with other drugs. Furthermore, they induce weight loss and are administered daily or weekly in an extended-release form.

Exenatide is a synthetic exendin-4 peptide variant. It is an analog of GLP-1 but is not metabolized by DPP-4, extending its action.

Another approach involves using the DPP-4 inhibitors that maximize the incretins' therapeutic efficacy.